The overall goal of this research is to study the role of leukocytes in the hemostatic and thrombotic process, with particular reference to the pathogenesis of clinically significant defibrination syndromes. Our demonstration that the chemotactic fragment of the fifth component of complement (C5a) stimulates leukocytes to generate tissue factor activity (TFa) will be further investigated. The role of C5 in the generation of TFa during stimulation by lipopolysaccharides (LPS) will be explored. The question of whether TFa generation requires the leukocyte 'oxygen burst' to complete the stimulatory process will also be studied. Conditions under which LPS and C5a bind to the leukocyte surface, as well as the requirements for such binding are to be investigated in relation to their stimulatory effect on the generation of TFa. Synergistic effects between stimuli such as C5a, f-met-leu-phe, gamma globulins and LPS on TFa and enzyme secretion by leukocytes will be explored in an attempt to identify the enzyme activating leukocyte TFa generation. Purfication of leukocyte tissue factor will be continued. Antibodies to leukocyte tissue factor will be raised. These antibodies, fluids and the localization of this antigen in tissues will help understand the physiopathogenetic process in which generation of leukocyte tissue factor activity occurs.